The proposed research involves the in vitro culture of primary fetal liver cells which are capable of producing erythropoietin in a scaled-up culture system. These cultures would be established in a controlled environmental system such that a precise definition and control of cell types(s), gas tensions and media components necessary for optimum erythropoietin biosynthesis would be supplied. The fetal liver cells would be grown as a monolayer on the surface of a microcarrier that is kept in suspension in culture media by stirring. Such cultures bring together the characteristics of both suspension culture and monolayer culture while retaining the advantages of both systems. This system should lead to a comprehension of the mechanism by which an erythropoietin generating cell monitors and controls erythropoiesis. In addition, these studies should allow for a better understanding of the control of erythropoietin production in man and for the determination of the practicality of producing large amounts of erythropoietin by tissue culture which are required for clinical use.